rs3212345

Positions:

• chr16-89915864-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000555427.1(MC1R):​c.-581+724T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.594 in 152,280 control chromosomes in the GnomAD database, including 29,946 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.59 (29946 hom., cov: 35)
• Consequence: MC1R ENST00000555427.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.264

Genes affected

MC1R (HGNC:6929): (melanocortin 1 receptor) This intronless gene encodes the receptor protein for melanocyte-stimulating hormone (MSH). The encoded protein, a seven pass transmembrane G protein coupled receptor, controls melanogenesis. Two types of melanin exist: red pheomelanin and black eumelanin. Gene mutations that lead to a loss in function are associated with increased pheomelanin production, which leads to lighter skin and hair color. Eumelanin is photoprotective but pheomelanin may contribute to UV-induced skin damage by generating free radicals upon UV radiation. Binding of MSH to its receptor activates the receptor and stimulates eumelanin synthesis. This receptor is a major determining factor in sun sensitivity and is a genetic risk factor for melanoma and non-melanoma skin cancer. Over 30 variant alleles have been identified which correlate with skin and hair color, providing evidence that this gene is an important component in determining normal human pigment variation. [provided by RefSeq, Jul 2008]

LOC124903759 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.895 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LOC124903759	XM_047435031.1	c.1040+724T>C		intron_variant			XP_047290987.1
LOC124903759	XM_047435032.1	c.1040+724T>C		intron_variant			XP_047290988.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MC1R	ENST00000555427.1	c.-581+724T>C		intron_variant		5		ENSP00000451760.1
MC1R	ENST00000639847.1	c.-581+724T>C		intron_variant		5		ENSP00000492011.1
ENSG00000267048	ENST00000570217.1	n.202-2012T>C		intron_variant		4

Frequencies

GnomAD3 genomes AF: 0.594 AC: 90388 AN: 152162 Hom.: 29890 Cov.: 35

Gnomad AFR AF: 0.865

Gnomad AMI AF: 0.356

Gnomad AMR AF: 0.587

Gnomad ASJ AF: 0.400

Gnomad EAS AF: 0.917

Gnomad SAS AF: 0.680

Gnomad FIN AF: 0.518

Gnomad MID AF: 0.589

Gnomad NFE AF: 0.426

Gnomad OTH AF: 0.548

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.594 AC: 90504 AN: 152280 Hom.: 29946 Cov.: 35 AF XY: 0.599 AC XY: 44617 AN XY: 74454

Gnomad4 AFR AF: 0.865

Gnomad4 AMR AF: 0.587

Gnomad4 ASJ AF: 0.400

Gnomad4 EAS AF: 0.917

Gnomad4 SAS AF: 0.678

Gnomad4 FIN AF: 0.518

Gnomad4 NFE AF: 0.426

Gnomad4 OTH AF: 0.551

Alfa AF: 0.487 Hom.: 4890

Bravo AF: 0.611

Asia WGS AF: 0.774 AC: 2693 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.31
DANN	Benign	0.33
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs3212345; hg19: chr16-89982272;